1/362. Juvenile form of dihydropteridine reductase deficiency in 2 Tunisian patients.Two brothers are described who had juvenile-onset DHPR deficiency. Both were considered normal until six years of age when they developed a fluctuating and progressive encephalopathy combining mental retardation, epilepsy, pyramidal, cerebellar and extrapyramidal signs.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
2/362. Respiratory chain complex III [correction of complex] in deficiency with pruritus: a novel vitamin responsive clinical feature.We report a child with an isolated complex III respiratory chain deficiency and global developmental delay who had severe pruritus with elevated plasma bile acid levels. A liver biopsy showed micronodular cirrhosis, and enzymologic evaluation demonstrated an isolated complex III deficiency in both liver and muscle. His pruritus improved and serum bile acid levels decreased after treatment with menadione and vitamin C.- - - - - - - - - - ranking = 1.2keywords = deficiency (Clic here for more details about this article) |
3/362. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study.BACKGROUND: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition. methods: We used 1H NMR spectroscopy to study serum and urine from the patient. RESULTS: The concentration of N, N-dimethylglycine (DMG) was increased approximately 100-fold in the serum and approximately 20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography-mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient. CONCLUSIONS: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.- - - - - - - - - - ranking = 0.6keywords = deficiency (Clic here for more details about this article) |
4/362. Pancreatic cancer and fibrinogen storage disease.BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. methods: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.- - - - - - - - - - ranking = 0.0003070952718461keywords = alpha (Clic here for more details about this article) |
5/362. An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets.Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the enzyme that catalyses the second reaction in the principal pathway for the synthesis of bile acids, has been reported to present with prolonged neonatal jaundice with the biopsy features of neonatal hepatitis. It has also been shown to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly, and steatorrhoea (a clinical picture resembling progressive familial intrahepatic cholestasis). This paper reports two children with 3beta-HSDH deficiency who developed rickets during infancy and did not develop clinically evident liver disease until the age of 3 years. bile acid replacement resulted in considerable clinical and biochemical improvement. The importance of thorough investigation of fat soluble vitamin deficiencies in infancy is emphasised.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
6/362. A severely affected infant with absence of cysteinyl leukotrienes in cerebrospinal fluid: further evidence that leukotriene c4-synthesis deficiency is a new neurometabolic disorder.leukotrienes are potent oxygenated metabolites derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. They comprise the cysteinyl leukotrienes (LTC4, LTD4, LTE4) and LTB4. The rate limiting step in the formation of cysteinyl leukotrienes is the conversion of LTA4 to LTC4 catalyzed by the enzyme LTC4 synthase. Recently, the first inborn error of leukotriene synthesis, LTC4-synthesis deficiency, has been identified in a patient with a fatal developmental syndrome. We report on an additional infant presenting with severe muscular hypotonia, symmetrical extension in the lower extremities and psychomotor retardation who died at the age of 6 months. Despite intensive investigations no specific diagnosis could be made. leukotrienes were subsequently analyzed in the cerebrospinal fluid. Concentrations of LTC4, LTD4 and LTE4 were below the detection limit (< 5 pg/ml) whereas LTB4 was found to be in the upper normal range. The absence of cysteinyl leukotrienes with normal LTB4 concentration in cerebrospinal fluid is unique and seems to be pathognomonic for LTC4-synthesis deficiency. Our patient most likely represents the second case described so far with this condition. This report provides further evidence that LTC4-synthesis deficiency represents a new neurometabolic disorder.- - - - - - - - - - ranking = 1.4keywords = deficiency (Clic here for more details about this article) |
7/362. Multiple acyl-coenzyme a dehydrogenase deficiency: diagnosis by acyl-carnitine analysis of a 12-year-old newborn screening card.We report a family who experienced an unexplained neonatal death. Twelve years after the death, we retrospectively diagnosed multiple acyl-coenzyme a dehydrogenase deficiency by demonstrating an abnormal acyl-carnitine profile in the child's archived newborn screening card, using tandem mass spectrometry.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
8/362. Inborn defects of fatty acid oxidation: a preventable cause of SIDS.Inborn errors of fatty acid oxidation, including medium chain acyl CoA dehydrogenase (MCAD) deficiency are readily detectable and treatable metabolic disorders in which recognition of symptoms is important. Symptoms occur when there is fasting, often associated with illness. If not diagnosed, these inborn errors of metabolism can result in sudden death classified as SIDS. These disorders can be diagnosed by ordering plasma or blood spot acylcarnitine profiles.- - - - - - - - - - ranking = 0.2keywords = deficiency (Clic here for more details about this article) |
9/362. hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics.hyperinsulinism-hyperammonemia syndrome (HHS) is a recently identified genetic disorder characterized by hyperinsulinemic hypoglycemia with concomitant hyperammonemia. In patients with HHS, activating mutations in the glutamate dehydrogenase (GDH) gene have been identified. GDH is a key enzyme linking glutamate metabolism with the Krebs cycle and catalyzes the conversion of glutamate to alpha-ketoglutarate. The activity of GDH is controlled by allosteric inhibition by GTP and, so far, all the mutations of HHS patients have been located within the GTP-binding site. Characteristically, GDH from these individuals have therefore normal basal activity in conjunction with a loss of GTP inhibition. In this study, however, we have identified a novel variant GDH in a patient with a more severe form of HHS. The mutation is located outside the GTP-binding site and the patient's GDH shows consistently higher activity, even in the absence of allosteric effectors. These results further support the hypothesis that the activating mutation of GDH is the cause of HHS. The mechanism leading to the activation of GDH, however, is not always related to the loss of GTP inhibition as was originally suggested.- - - - - - - - - - ranking = 0.0003070952718461keywords = alpha (Clic here for more details about this article) |
10/362. Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency.An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.- - - - - - - - - - ranking = 0.8keywords = deficiency (Clic here for more details about this article) |
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